Indiana University Bloomington

Faming Zhang Research Group

Research

Structural Biology in Obesity Research

  • 97 Million Americans Are Overweight Or Obese
  • Indiana is the Land of the Fat
  • This Condition DramaticallyRaises Their Risk Of
    • Type II Diabetes
    • Hypertension
    • Coronary Heart Disease
    • Stroke
    • Gallbladder Disease
    • Osteoarthritis
    • Cancers Of The:
      • Breast, Prostate,
      • Endometrium and Colon

Chemical Genomics in TGFβ Signaling and Cancer

TGFβ receptor signal transduction pathway. TGFβ and related polypeptides constitute the largest cytokine family that regulates a diverse array of cellular processes such as proliferation, differentiation, adhesion and apoptosis. Cell surface binding of TGFβ leads to the formation of a heteromeric complex of type I and type II receptors (TβRI & TβRII), each of which are transmembrane-spanning proteins featuring a serine/threonine kinase domain. Downstream signal transduction is mediated by the TβR kinase domain through the phosphorylation of Smad proteins, which as oligomeric complexes translocate to the nucleus and regulate gene expression via association with DNA transcription factors. The TGFβ signaling pathway plays a role in number of disease states involving inflammation, angiogenesis, AlzheimerÕs disease, hypertension and cancer.

Structure-Based Therapeutic Protein Design and Optimization

Glucogan-like peptide-1 (GLP-1) is a potent blood glucose-lowering hormone now under investigation for use as a therapeutic agent in the treatment of type 2 diabetes mellitus. GLP-1 and it's analogue Exendin bind with high affinity to its GPCRs located on pancreatic beta-cells, and it exerts insulinotropic actions that include the stimulation of insulin gene transcription, insulin biosynthesis, and insulin secretion. Recent studies have demonstrated that GLP-1 also regulates cell proliferation, differentiation, and apoptosis and it may represent a potential novel therapeutics for intervention in Alzheimer's disease (AD) and potentially other central and peripheral neurodegenerative conditions. GLP-1 is rapidly degraded by protease and has an extremely short half-life. The development of GLP-1 as therapeutic agent is focused on its protease resistance and chemical stability.